ObjectiveTo generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets.MethodsA validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017.ResultsThe estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1–310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1–451.6) for women and 159.7 (95% CI 158.7–160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017.ConclusionThe estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

Context: Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention.Objective: To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD. Design, Setting, and Participants: We conducted the first ever pooled analysis of PD combining individuallevel data from 8 US case-control and 3 cohort studies (Nurses' Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age-and sex-matched risk sets. Main Outcome Measure: Incident PD.Results: We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (Ͼ75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects. Conclusions: Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.

Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.

Background and Purpose: Subarachnoid hemorrhage remains a devastating disease. Identification of etiologic risk factors would allow the possibility of prevention.Methods: We conducted a population-based case-control study in King County, Washington. Patients whose bleeds originated from a source other than an aneurysm were excluded. Two age-and gendermatched control subjects were identified for each case through random digit telephone dialing. A standardized in-person interview was conducted with the patient whenever possible, a proxy respondent for the case in all instances, the two control subjects, and their proxies. Analyses involved conditional logistic regression taking into account matching on age, gender and respondent type.Results: Over 2 years, 169 cases were identified, and 149 participated in the case-control study. Compared with those who never smoked, the odds ratio for current heavy smokers (>20 cigarettes/day) was 11.1 (95% confidence interval [CI], 5.0-24.9); for current light smokers (<20 cigarettes/day), 4.1 (95% CI, 2.3-7.3); and for former smokers, 1.8 (95% CI, 1.0-3.2). The risk associated with smoking was greatest in the 3 hours after a cigarette (odds ratio [OR] =7.0; 95% CI, 3.7-13.1) and then fell, not reaching the risk in those who had never smoked until more than 10 years had passed since the last cigarette. Heavy alcohol use (>2 drinks/day) was also associated with bleeds (OR=2.2; 95% CI, 0.9-5.1, after adjusting for smoking status). These associations were not substantially altered after adjusting for several possible confounding factors, including a history of hypertension.Conclusions: Cigarette smoking and heavy alcohol use are associated with the occurrence of subarachnoid hemorrhage. (Stroke 1992;23:1242~1249) KEY WORDS • alcohol drinking • cigarette smoking • epidemiology • subarachnoid hemorrhage

This study used the Wechsler Adult Intelligence Scale and an expanded Halstead-Reitan Battery (HRB) to assess neuropsychological functioning in 100 patients who had relapsing-remitting or chronic-progressive courses of multiple sclerosis (MS). The patients were representative of a regional MS clinic population and were clinically stable at the times of testing. Both MS subgroups showed significant neuropsychological impairment, relative to a normal comparison group (N = 100), but chronic-progressive MS was associated with greater impairment in each major ability domain (cognitive, sensory, motor). In particular, only minimal cognitive impairment was noted in the relapsing-remitting MS subgroup, whereas the chronic-progressive subgroup showed impairment on virtually all cognitive test measures from the expanded HRB. Degree of neuropsychological impairment was significantly correlated with MS duration but was unrelated to medication status. The MS subgroup differences on the test battery could not be attributed to duration of illness, indicating that disease course is an important independent determinant of neuropsychological impairment in MS. Disability ratings from clinical neurological examinations were highly correlated with motor and sensory performances on neuropsychological testing, but clinical exams were inadequate in predicting the patients' cognitive status.

To determine if exclusive breastfeeding protects against postpartum relapses of multiple sclerosis (MS) and, if so, whether this protection is related to prolonged lactational amenorrhea.Design: We conducted structured interviews to assess clinical, menstrual, and breastfeeding history during each trimester and 2, 4, 6, 9, and 12 months postpartum and collected neurological examination findings from the treating physicians of women with MS. Hazards ratios (HRs) were adjusted for measures of disease severity and age.

had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

This population-based case-control study was conducted in three countries in western Washington State to evaluate associations between workplace exposures and the risk of amyotrophic lateral sclerosis (ALS). Cases (n = 174) were all newly diagnosed with ALS by neurologists during 1990-1994, and controls (n = 348), who were matched according to age (+/-5 years) and sex, were identified via random-digit dialing or Medicare enrollment files. Four industrial hygienists blindly assessed detailed lifetime job histories for exposures to metals, solvents, and agricultural chemicals. Case-control comparisons were made for jobs held between 15 years of age and 10 years prior to the cases' dates of diagnosis. After adjustment for age and education, ever exposure to agricultural chemicals was associated with ALS (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.5); this association was observed separately in men (OR = 2.4, 95% CI 1.2-4.8) but not in women (OR = 0.9, 95% CI 0.2-3.8). Among men, the odds ratio for low exposure to agricultural chemicals (below the median level for exposed controls) relative to no exposure was 1.5 (95% CI 0.4-5.3), and for high exposure, it was 2.8 (95% CI 1.3-6.1) (p for trend = 0.03). Similar analyses based on the panel's assessment of exposures to metals and solvents showed no associations. These findings suggest an association between ALS and agricultural chemicals in men.